Determination Of Blood Levels Research Articles

Effect of CYP3A5*3 genotype on exposure and efficacy of quetiapine: A retrospective, cohort study

BackgroundThe involvement of cytochrome P450 3A5 (CYP3A5) in the metabolism of quetiapine has been proposed, though conclusive evidence is lacking. This study aimed to quantitatively assess the impact of CYP3A5 genetic variability on quetiapine exposure in a Chinese patient population. MethodsPatient data were retrospectively collected from the database of the Mental Health Centre at the First Hospital of Hebei Medical University, covering the period from September 1, 2019, to July 1, 2023. The study included patients genotyped for CYP3A5 who were treated with quetiapine. Inclusion criteria for the analysis of pharmacokinetic parameters, such as serum concentrations of the drug and its metabolites, included oral administration of quetiapine, availability of information on the prescribed daily dose and concomitant medications, and the determination of steady-state blood levels at the time of sampling (after at least 3 days of continuous administration at the same dose). Exclusion criteria comprised polypharmacy with known CYP3A4 inducers or inhibitors, as well as patients with hepatic or renal insufficiency. The primary endpoint was the exposure to quetiapine and N-dealkylquetiapine, measured using dose-corrected concentrations (C/D). The secondary endpoint was the metabolism of quetiapine to N-dealkylquetiapine, assessed by the ratio of metabolite to parent drug concentrations. The third endpoint is the differences in adverse reactions, QTc intervals, and biochemical parameters among patients with different CYP3A5 genotypes. ResultBased on the inclusion and exclusion criteria, clinical data from 207 patients were ultimately included in the study. Of these, 20 patients had the CYP3A5*1/*1 genotype, 78 had the CYP3A5*1/*3 genotype, and 109 had the CYP3A5*3/*3 genotype.The CYP3A5*3 variant was found to significantly impact the metabolism of quetiapine. The C/D values for both quetiapine and dealkylated quetiapine were notably higher in individuals with the *3/*3 genotype compared to those with the *1/*1 and *1/*3 genotypes (P1 <0.001 and P2 = 0.002, respectively). A comparison of the variability in metabolic ratios among different genotype groups revealed no significant difference (P = 0.067). However, a post hoc analysis indicated that the metabolic ratio in poor metabolizers was significantly lower than that in intermediate metabolizers (P = 0.021). The analysis of adverse reaction incidence and QTc intervals among different genotypes showed no statistically significant differences (P = 0.652, P = 0.486). However, comparison of biochemical parameters across different genotype groups revealed that alanine aminotransferase, uric acid, hemoglobin, and gamma-glutamyl transferase levels were significantly higher in patients with the CYP3A5*3/*3 genotype compared to those with the CYP3A5*1/*1 and CYP3A5*1/*3 genotypes. ConclusionThe results indicated that the genetic polymorphism of CYP3A5*3 significantly influences the metabolism of quetiapine. Specifically, carriers of the CYP3A5*3/*3 genotype exhibited higher blood levels of quetiapine, with a greater likelihood of these levels exceeding the therapeutic range. This finding underscores the need for clinicians to carefully monitor and potentially adjust the dosage for patients with this genotype to avoid adverse effects. This finding underscores the need for clinicians to pay special attention to the efficacy and occurrence of adverse reactions when prescribing quetiapine to patients carrying the CYP3A5*3/*3 genotype.

Assessment of immune status markers during occupational lead exposure

The immune system is sensitive to the effects of environmental factors, and according to numerous studies, lead has an immunotoxic effect. At the same time, there is evidence of the multidirectional nature of the impact of lead on the immune system, determined by the degree of exposure to this heavy metal, which makes it current to study changes in immunological markers in workers of a modern lead recycling plant, taking into account levels and complexity of exposure. In the era of personalized medicine, monitoring the potential influence of occupational factors exposure on the immune system can facilitate a personalized approach to the prevention of work-related health conditions. The aim of the study: to evaluate changes in immune status markers among employees of lead recycling plant. The main group – 62 men working at a lead recycling plant, the control group – 47 men not exposed to occupational factors. Laboratory examination included a determination of the lead blood level, a clinical blood test, the serum levels of IL- 1â, IL- 10, IL- 8, MCP-1, C3 and C4 complement components, IgA, IgM, IgG. In the main group, compared to the control group, a higher number of neutrophils, lymphocytes, monocytes, higher levels of IL-8, C3 and C4 components of the complement system, and lower levels of IgM were detected. In the main group, the following changes in markers were significantly more often detected in comparison with reference values: an increase in the C3 component of complement (51.6% in the main group compared to 12.5% in the control group), decreased IgG (24.2% compared to 6.2%) and increased IgA (22.6% compared to 6.2%). Associations were identified between the lead blood level and the number of lymphocytes, the level of IgG, between work experience in contact with lead and the level of MCP-1 and C3 complement components. The results of the studies revealed the presence of changes in the immune status markers of workers at a lead recycling plant, which demonstrate a proinflammatory effect of lead and an influence on the humoral immune status. The identified changes in immunological parameters may underlie the mechanisms of formation of pathological conditions associated with lead exposure, which determines the relevance of continuing research to assess dynamic changes in immunological parameters and develop a system for monitoring the immune status of workers exposed to lead and its compounds to optimize preventive measures.

Mood disorders and suicide: pilot study on postmortem toxicologic evidence and adherence to psychiatric therapy by determining blood levels of medications.

Suicide is one of the leading causes of death today, and among all mental illness, mood disorders account for one of the main risk factors. It is well known and proven that suicides are very common among people undergoing treatment and prescribed psychiatric medication. So far, however, there have only been a few studies dealing with this particular phenomenon. For this reason, autopsy patients who died by suicide, suffered from a mood disorder, and were known to be taking psychiatric medication at the time of death were selected for this study. The blood and urine samples taken during the autopsy underwent toxicological analysis and the results were compared with the prescribed therapy. A total of 22 people were included in the study: 12 presenting with depression and 10 with bipolar disorder. The toxicological analysis revealed that only 6 cases (27%) showed a qualitative match with the prescribed medication. In 5 cases (22.7%) the medication was only partially complied with and in 11 cases (50%) it was not complied with at all. Furthermore, even when medication was present, the value was often below the therapeutic range. Overall, more than 70% of the test subjects adhered to their medication only partially or not at all. Since treatment adherence is considered as a key factor in reducing the risk of suicide, this inevitably raises relevant clinical and forensic questions. Against this background, prospective monitoring of post-mortem medication levels in suicidal individuals and synergistic collaboration between clinicians and forensic pathologists could help to evaluate the effectiveness of specific medical interventions, highlight existing critical problems and develop new approaches to suicide prevention.

Cardiac biomarkers as tools in the prediction and diagnosis of traumatic pericarditis and traumatic reticuloperitonitis in cattle and buffaloes

BackgroundIn the livestock industry, Foreign Body Syndrome is a devastating disease condition. Feeding management, lacking of food discrimination, and eating chopped food increase the risk of swallowing sharp foreign bodies in bovine species. In addition to the honeycomb cells shape of the reticulum, the contractions of the reticular wall, gravid uterine pressure, and parturition efforts, foreign bodies can penetrate the reticular wall, causing cascade of problems including traumatic reticulitis, traumatic reticuloperitonitis, and traumatic pericarditis. The present study was carried out to evaluate the diagnostic significance of cardiac troponin I rapid test cassette and other cardiac biomarkers including serum cardiac troponin I (cTn I), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase enzyme (AST), in confirmed cases of traumatic pericarditis (TP) and/or traumatic reticuleoperitonitis (TRP) in cattle and buffaloes.MethodsA total number of 30 animals (22 cattle and 8 buffaloes) with different signs such as anorexia, jugular distension, brisket edema, and signs of pain (reluctance to move, arching back, and abduction of the forelimbs) were included in the present study. Based on case history, clinical signs, ferroscopic, pericardiocentesis, radiographic and ultrasonographic examinations, TP were confirmed in cattle (n = 10) and buffaloes (n = 8) while TRP were confirmed only in cattle (n = 12). Additionally, 20 clinically healthy animals (n = 10 cattle and 10 buffaloes) were used as a control group. Blood samples were collected for determination of blood level of Tn-I, and activity of CK-MB, LDH, and AST.ResultsThe obtained results revealed a highly significant increase in serum cTn I in diseased cattle with TP and TRP (P = 0.00), while buffaloes with TP showed no significant changes in serum cTn I (P = 0.111). Both diseased cattle and buffaloes showed increased serum activities of CK-MB, AST, and LDH enzyme. On the other hand, cardiac troponin I rapid test cassette failed to detect cTn I in diseased animals.ConclusionThe study concluded that the cardiac troponin I rapid test cassette did not have a diagnostic significance and could not be used as a point-of-care under field condition for diagnosis of TP and TRP in large ruminants. However, the serum troponin I level is helpful in diagnosis of TP and TRP in cattle. Although cardiac biomarkers have some diagnostic values in TP and TRP, the traditional diagnostic methods (clinical, radiography and ultrasonography examinations) are crucial for thorough evaluation of TP/TRP cases in bovine.

Clinical significance of procollagen type III N-terminal peptide in patients with alcoholic liver disease

Background. Alcoholic liver disease (ALD) – is a disease that leads to the development of liver cirrhosis (LC) with a high mortality rate. N-terminal type lll procollagen peptide (PIIINP) is one of the optimal biomarkers for assessing fibrogenesis.Objective: to determine the clinical significance of PIIINP blood level in patients with ALD.Materials and methods. 97 patients with ALD were examined. The age of the patients was 48,5±9,9 years, there were 30 women, 67 men. Steatosis was diagnosed in 12 patients, 11 – alcoholic hepatitis (AH), 74 – LC. In group with LC, 16 patients was diagnosed AH against confirmed cirrhosis. PIIINP blood level determined by ELISA. Control group consisted of 22 healthy volunteers who have not consumed alcohol in hepatotoxic doses.Results. In all patients, PIIINP blood level was increased. In steatosis PIIINP slightly increased the norm, indicating the beginning of fibrogenesis. In LC, PIIINP blood level was higher than in patients with steatosis, which reflected increasing of fibrosis and progression of the disease. The highest levels of PIIINP were observed in cases with AH. Levels PIIINP in patients with AH but without LC and in patients with AH against the background of the formed LC did not differ. In Maddray index of more than 32 (9 patients), the PIIINP level was higher than in 18 patients with index values &lt;32, which confirmed the role of AH in development of fibrosis and decompensation of liver function.Conclusion. Determination of PIIINP blood level in patients with ALD will allow predict the activity of fibrogenesis and the severity of subsequent changes in liver tissue. In cases of severe AH, PIIINP may be an additional criterion determining the severity and prognosis of hepatitis outcomes.

Evaluation of CYP2C19 Genetic Variant and Its Lack of Association with Valproic Acid Plasma Concentrations Among Zhuang and Han Schizophrenia Patients in Guangxi.

To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations. Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 *1, *2, and *3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression. The study identified five CYP2C19 genotypes at the *2 and *3 loci, with the *3/*3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18-60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age. In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.

Effects of Simulated Microgravity on Rat Reproductive System: Potential Benefits of Vitamin D3 Intervention.

Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system.Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination.Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations.

Standardization and validation of a high-efficiency liquid chromatography with a diode-array detector (HPLC-DAD) for voriconazole blood level determination.

A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies. To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification. We used an Agilent HPLC™ series-1200 equipment with a UVdiode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent). We used voriconazole as the primary control and posaconazole as an internal control. We performed the validation following the Food and Drug Administration (FDA) recommendations. The best chromatographic conditions were: Column temperature of 25°C, UV variable wavelength detection at 256 nm for voriconazole and 261 nm for posaconazole (internal standard); 50 μl of injection volume, 0,8 ml/min volume flow, 10 minutes of run time, and mobile phase of acetonitrile:water (60:40). Finally, retention times were 3.13 for voriconazole and 5.16 minutes for posaconazole. Quantification range varied from 0.125 μg/ml to 16 μg/ml. The selectivity and chromatographic purity of the obtained signal, the detection limits, and the standardized quantification make this method an excellent tool for the therapeutic monitoring of patients treated with voriconazole.

Dynamics of the functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy

The aim. To evaluate the dynamics of metabolic status, functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy (MGT). Materials and methods. 40 menopausal women were examined, of which 25 patients with metabolic syndrome with an average age of 51.2 ± 1.2 years and 15 practically healthy women of 50.2 ± 1.9 years. anamnesis was collected, the presence of vasomotor symptoms was assessed, anthropometric data was measured with the calculation of body mass index, laboratory examination, including determination of blood levels of sex hormones, functional liver tests, metabolic parameters and markers of endothelial dysfunction- endothelin-1, vascular endothelial growth factor, the number of desquamated endotheliocytes and the activity of Willebrand factor, instrumental examination, including ultrasound examination of the liver and assessment of the vascular response to local heating on the Microtest device (Russia), as well as calculation of the Hepatic steatosis index (HSI). Results. In patients with metabolic syndrome in menopause, vasomotor symptoms, complaints of dysuria, dyspeptic phenomena were observed, an increase in blood pressure was recorded in 60%, an increase in Kurlov’s ordinates in 24%, 36% were overweight, 64% were obese 1-2 degrees. According to ultrasound, liver steatosis was verified in 76% of patients, the HSI index &gt;36.0 was in all women with MS. Against the background of estrogen deficiency, the course of menopause in women was accompanied by insulin resistance, dyslipidemia, increased alkaline phosphatase levels in 28% of individuals and endothelial dysfunction with impaired physiological response to local heating, increased vascular tone, increased thrombogenic potential of the vascular wall and activation of angiogenesis mechanisms. Conclusion: MGT with Femoston ® 1 in continuous mode in women with metabolic syndrome reduces the severity of menopausal syndrome, insulin resistance and liver steatosis, improves anthropometric parameters and functional characteristics of the liver and endothelium, which reduces the risk of cardiovascular events in this risk group.

Micronutrients deficiencies (poor levels of antioxidants Vitamin A and Vitamin C) and Academic Performance of Selected Young Girls in Sokoto, Nigeria

It is widely stressed that girl-child education is good; and girls could only learn properly if they are fed well. Levels of micronutrients such as antioxidants vitamins A and C could lead to poor brain or nervous system functions. The objective of this work was to evaluate the relationship between Micronutrients deficiencies (poor levels of antioxidants Vitamin A and Vitamin C) and academic performance of selected young girls in Sokoto, Nigeria. This work determined blood levels of vitamin A and C in 250 young girls in Sokoto using standard methods and materials of analytical grade. A semi experimental study involving 40 selected study participants was done. An exploration of academic performance of subjects that are with enough vitamin C and A and their counterparts was done using assessment. This study shows that, the girls with normal levels of antioxidants vitamins A and C scored a mean mark (55.0+ 13.015) more than those with poor levels (35.63+12.63) (p&lt;0.05). This signifies that nutritional concerted interventions are needed. Nutritional education, soil fertilization, bio fortification, and relations could be used for improving public diet in the state.

Rapid Clozapine Blood Level Determination in a National Health Service Trust

AimsThe use of clozapine demands regular monitoring of patients’ clozapine blood levels. Assays are usually performed in a central laboratory with results available only after several days. The South London and Maudsley NHS Trust wanted to implement a clozapine Point-of-Care (POC) capillary blood test that would provide the benefits of immediate results.MethodsThe MyCare Insite, a small (2.2 kg) tabletop analyser was used. The Insite can readily be connected to electronic health records. Insite device has been fully validated but to achieve the benefit of clozapine POC testing, other factors beyond the test validation needed to be considered. We developed tools, software, and processes to guide health professionals on why and when to measure clozapine blood levels, on what to do with test results, and systems for documentation and tracking of patients’ test results. In addition, the device supplier conducted staff training to ensure consistent and correct testing. Finally, users were certified as qualified based on demonstrated proficiency.ResultsWe have fully implemented POC capillary clozapine testing across four geographic sites.. Patients and staff preferred capillary finger stick testing over venous draws. Patients’ engagement with their results was better than with laboratory testing. Real-time testing for adherence was possible for patients admitted on clozapine. It was also possible to make rapid dose adjustments based on near immediate plasma level results. Patient safety was increased since toxic levels could be quickly detected. Clinical decision-making was expedited as results were available immediately (&lt; 7 minutes). The utility of the testing meant that the length of hospital stays was reduced as discharges were not delayed pending a laboratory result.ConclusionClozapine POC blood level testing was successfully implemented at our institution achieving the expected benefits of clozapine POC testing with near immediate results. The new process improves clozapine management, patient engagement and reduces inpatient bed stays.

Ferritin, IL-6 and human-beta-defensin-1 as prognostic markers of the course severity and treatment effectiveness of pulmonary tuberculosis

Current methods of investigation in TB patients, namely sputum microscopy, culture, and molecular genetic methods, although well-studied, have a number of disadvantages, such as low sensitivity, long time required to obtain results, or high cost. Because of this, the search for alternative diagnostic tools and methods for predicting the course and effectiveness of treatment in patients with tuberculosis becomes relevant. In this study, ferritin, interleukin-6 (IL-6), and human-beta-defensin-1 (HBD-1) were selected for comparison of prognostic performance.&#x0D; Objective — to investigate the dynamics of ferritin, IL-6, and human-beta-defensin-1 levels against the background of the intensive phase of pulmonary tuberculosis therapy and to identify the most effective marker for predicting the effectiveness of treatment.&#x0D; Materials and methods. 100 patients with pulmonary tuberculosis and 20 healthy individuals were included in the study. Examination of patients was carried out according to the current standards of providing medical care to tuberculosis patients. In addition, the patients' fasting blood ferritin, IL-6 and HBD-1 levels were determined at the beginning of treatment and after 60 days. Healthy individuals from the control group had a single determination of ferritin, IL-6 and HBD-1 blood levels on an empty stomach. &#x0D; Results and discussion. At the beginning of treatment, the ferritin level was significantly lower (95.95 ± ± 8.68) ng/ml in patients who later effectively completed the intensive phase of anti-tuberculosis treatment than in patients with ineffective intensive phase of treatment (152.27 ± 8.85) ng/ml. The same trend persisted after 60 days: in the effective intensive phase — (123.87 ± 13.39) ng/ml, in the ineffective one — (239.76 ± 12.91) ng/ml, p &lt; 0.05. In effective intensive phase of antituberculosis treatment, the level of IL-6 was significantly lower. Thus, at the beginning of treatment, it was (82.59 ± 6.89) pg/ml in patients with an effective intensive phase of treatment and (146.42 ± 8.04) pg/ml in patients with ineffective intensive treatment phase. After 60 days, it was (48.88 ± 4.19) pg/ml in patients with an effective intensive phase of treatment and (142.89 ± 9.11) pg/ml in patients with ineffective intensive treatment phase, p &lt; 0.05. The level of HBD-1 was higher when the intensive phase of antituberculosis therapy was ineffective, as when measured at the beginning of treatment (effective intensive phase — (18.71 ± 3.31) pg/ml, ineffective intensive phase — (32.79 ± 8.31) pg/ml), as well as when measured after 60 days (effective intensive phase — (19.93 ± 3.58) pg/ml, ineffective intensive phase — (42.92 ± 12.99) pg/ml, p &lt; 0.05).&#x0D; Conclusions. Levels of ferritin, IL-6 and HBD-1 are significantly increased in tuberculosis patients compared to healthy individuals, which allows them to be considered as markers of tuberculosis inflammation. Higher concentrations of these markers, both at the beginning of treatment and after 60 doses, are predictors of failure of antituberculosis therapy. The strongest relationship between the studied markers and parameters of the severity of the tuberculosis process is observed in the study of HBD-1, which allows us to consider it as the most effective marker of the severity of the course among presented ones.

BLOOD LEVELS OF INTERLEUKIN-17A IN PATIENTS WITH ARTERIAL HYPERTENSION AND ITS RELATIONSHIP WITH THE CHARACTERISTICS OF THE COURSE OF DISEASE

Objective: One of the most important links in the pathogenesis of arterial hypertension (AH) is currently considered to be the activation of subclinical inflammation. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes. The objective of the study was to evaluate the changes in blood levels of IL-17A in patients with AH and its relationship with the characteristics of the course of the disease. Design and method: The study involved 65 patients with grade 2-3 AH (34 men and 31 women aged 37 to 59 years) and 22 practically healthy individuals in the control group (12 men and 10 women aged 19 to 47 years). Patients were examined using standard clinical, laboratory and instrumental methods. The scope of the study also included the determination of blood levels of IL-17A and highly sensitive C-reactive protein (hsCRP) by the enzyme immunoassay. Examination of all patients and persons of the control group was carried out before the start of the war in Ukraine. Results: A significant increase in blood levels of IL-17A was established in general in the group of patients with 2-3 degree AH ((7.12 [4.74;10.67]) pg/mL, P &lt;0.05) in comparison with practically healthy individuals ((3.24 [0,96;4,59]) pg/mL). The highest blood levels of IL-17A were found in patients with AH with a more pronounced increase in blood pressure (BP) up to the 3rd degree of AH ((9.87 [5.98;13.56]) pg/mL, P&lt;0.05) compared with the levels of this factor in patients with 2nd degree of AH ((5.85 [3,66;8,12]) pg/mL). Significant positive correlations were found between blood levels of IL-17A and hsCRP (P = 0,023), left ventricular mass index (P = 0,027) and systolic BP (P = 0,036). Conclusions: In patients with grade 2-3 AH, a significant increase in blood levels of proinflammatory cytokine IL-17A and its relationship with indicators of activation of subclinical inflammation, the severity of hypertrophic remodeling of the heart, and the severity of hypertension were found.

Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression

BackgroundAffective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance. PurposeIn the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020). MethodsStudy design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered. ResultsNon-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores. ConclusionsCarriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.

Impact of the Junction Adhesion Molecule-A on Asthma.

Junctional adhesion molecule (JAM)-A is an immunoglobulin-like molecule that colocalizes with tight junctions (TJs) in the endothelium and epithelium. It is also found in blood leukocytes and platelets. The biological significance of JAM-A in asthma, as well as its clinical potential as a therapeutic target, are not well understood. The aim of this study was to elucidate the role of JAM-A in a mouse model of asthma, and to determine blood levels of JAM-A in asthmatic patients. Mice sensitized and challenged with ovalbumin (OVA) or saline were used to investigate the role of JAM-A in the pathogenesis of bronchial asthma. In addition, JAM-A levels were measured in the plasma of asthmatic patients and healthy controls. The relationships between JAM-A and clinical variables in patients with asthma were also examined. Plasma JAM-A levels were higher in asthma patients (n=19) than in healthy controls (n=12). In asthma patients, the JAM-A levels correlated with forced expiratory volume in 1 second (FEV1%), FEV1/forced vital capacity (FVC), and the blood lymphocyte proportion. JAM-A, phospho-JNK, and phospho-ERK protein expressions in lung tissue were significantly higher in OVA/OVA mice than in control mice. In human bronchial epithelial cells treated with house dust mite extracts for 4 h, 8 h, and 24 h, the JAM-A, phospho-JNK, and phospho-ERK expressions were increased, as shown by Western blotting, while the transepithelial electrical resistance was reduced. These results suggest that JAM-A is involved in the pathogenesis of asthma, and may be a marker for asthma.

A Non-radiometric Approach to Determine Tissue Vascular Blood Volume in Biodistribution Studies.

The aim of this research was to develop a reliable non-radiometric method to measure the residual blood in tissue without the need for perfusion or radiometric measurements in biodistribution studies. It was found that the perfusion method not only was ineffective in removing blood from tissue, but also introduced additional variability in the determination of tissue drug exposure and was not reproducible across studies. In addition, the use of hemoglobin as an endogenous protein and biomarker for tissue blood content was studied and it was found that hemoglobin measurement in tissue was not a reliable and effective approach for determination of residual blood level in tissue. To evaluate an alternative method for addressing the tissue blood level in biodistribution studies, animals were dosed with a Residual Blood Determinant Reagent (RBDR) 5min prior to tissue harvesting. The level of RBDR, an exogenous protein, was measured in whole blood homogenate and in tissue lysate. Based on the level of the RBDR, the vascular blood volume (VBV) in tissue was calculated and then the tissue exposures were corrected based on the blood volumes. The tissue VBVs measured by the RBDR method were comparable with the literature values obtained by radiometric measurements.

DYNAMICS OF GALECTIN-3 LEVELS IN PATIENTS WITH ACUTE CORONARY SYNDROMES AND 2 TYPE DIABETES MELLITUS UNDER THE INFLUENCE OF EMPAGLIFLOZIN AND TRIMETAZIDINE

It is known that cardiovascular diseases (CVD) will continue to occupy a prominent place in the structure of morbidity, mortality and disability of the world population. Patients with diabetes (DM) are several times more likely to develop adverse cardiovascular events. In recent years, markers of inflammation, which are involved in the progression of atherosclerosis, have been studied. One of them is galectin-3, which is involved in cell differentiation, fibrosis and immune inflammation. Data on changes in the activity of galectin-3 concentration in patients with ACS are scarce and contradictory.&#x0D; The purpose is to study the dynamics of galectin-3 content in the blood of patients with acute coronary syndromes (ACS) and concomitant type 2 diabetes in the course of treatment using empagliflozin and trimetazidine.&#x0D; Material and methods. At the first stage, 124 patients with ACS were examined; the control group consisted of 30 practically healthy people. The second stage of the study included 93 patients with ACS and diabetes, who, depending on the treatment strategy, were divided into 3 subgroups: 29 patients who were prescribed therapy in accordance with the guidelines; 30 patients who were additionally prescribed empagliflozin at a dose of 10 mg per day; 34 patients were prescribed a combination of empagliflozin and trimetazidine at a dose of 35 mg twice a day in addition to optimal drug therapy. All patients were examined upon admission before starting the course of treatment. Repeated examinations were carried out on the 28th day and after 3 months. Galectin-3 content was determined by enzyme- linked immunosorbent assay (ELISA). General laboratory tests were carried out, as well as determination of blood levels of brain natriuretic peptide (NT - proBNP), highly sensitive C-reactive protein (hs CRP), glycosylated hemoglobin. The severity of coronary artery damage was calculated according to the Gensini scale. Statistical processing received data were collected using the standard package of the "Statistics 12" program. The data were considered reliable at p &lt;0.05.&#x0D; Research results. The average age of the examined patients was (63.4 ± 5.21) years. The average values of galectin-3 levels in the blood of patients with ACS without type 2 diabetes were: (28.23 ± 3.17) ng /ml, and with concomitant DM – (35.67 ± 2.98) ng /ml (p &lt;0.01), which was 3.18 and 4.01 times higher indicators of control groups : (8.89 ± 3.41) ng /ml, respectively (p &lt;0.001).&#x0D; By the multivariate method regressive linear modeling noted dependence between levels of galectin-3 in patients with ACS with type DM and the number of leukocytes, levels hsCRP, NT- proBNP, creatinine, glucose, glycosylated hemoglobin and severity of coronary artery damage due to the Gensini scale.&#x0D; At the end of study, on the 28th day, a significant decrease in the content of galectin-3 in the blood was observed only in the group of patients who were additionally prescribed a combination of empagliflozin and trimetazidine - by 22.13% of the initial values. At the end of observation (3rd month) in all groups of examined patients, the average values of the specified indicator decreased to the same extent, however, they did not return to normal values.&#x0D; Conclusions:&#x0D; &#x0D; Concomitant type 2 diabetes significantly affects the increase of galectin-3 levels in the blood of patients with acute coronary syndrome.&#x0D; The additional appointment of trimetazidine leads to a faster decrease in the levels of galectin-3 in the blood of patients.&#x0D;

A case report: Fatal intoxication by simultaneous abuse of cocaine and ethyl alcohol

Concurrent use of cocaine and ethyl alcohol leads to the formation of cocaethylene. This substance has the same cardiotoxic effects as cocaine, while being eliminated three times slower, which prolongs the harmful effect on the heart. It is known that cocaine alone increases heart rate and blood pressure, but the alcohol-cocaine mixture increases them even more and the risk of sudden death from cardiac arrest is 22% greater. We present herein the case of a 33-year-old young man who died suddenly from cardiac arrest. According to informations provided by the medical examiner, the deceases was addicted to cocaine and other unspecified narcotics. In order to confirm the toxic death, a toxicological screening is carried out by a gas chromatography-mass spectrometry method (GC-MS, Perkin Elmer), as well as a determination of the alcohol blood level by gas chromatography flame ionisation detector (GC-FID, Perkin Elmer). The result of the alcohol blood level came back positive with a rate equal to 02.16 g/L. The toxicological screening revealed the presence of cocaine, cocaethylene, methylecgonidine and cotinine. No other substance, toxic, medicinal or narcotic, was detected. The results of the toxicological analysis carried out in our laboratory allowed the forensic experts to confirm the cause of death by the concomitant use of cocaine-ethyl alcohol mixture.

D-amino Acids as Novel Blood-based Biomarkers.

D-amino acids are present in the human body originating from diet, bacterial flora, and endogenous synthesis (at least for D-serine and, probably, D-aspartate). D-amino acids are involved in important physiological processes (e.g., D-serine and D-aspartate act on the N-methyl-D-aspartate receptor as co-agonist and agonist, respectively) and increasing evidence links D-amino acids to different pathological states. Determination of D-amino acids levels in blood is mainly based on enantiomeric separations by high performance liquid chromatography. Because of the low amount of D-enantiomers compared to the corresponding L-amino acids and the high background noise associated with biological matrices, positive and negative controls are absolutely required to obtain reliable values. Altered levels of D-serine in blood have been reported in several neurological and psychiatric disorders: it has been proposed as promising biomarker in schizophrenia, Alzheimer's disease, and amyotrophic lateral sclerosis. Indeed, D-serine levels seem an appropriate predictor of anti-depressant response in major depressive disorder and posttraumatic stress disorder, as well as a prognostic biomarker of early cognitive decline, especially when considering D-serine and D-proline levels simultaneously. Furthermore, D-amino acids seem useful biomarkers for pathologies not related to the central nervous system, such as pancreatic cancer and chronic kidney diseases. This is the first review focusing on the determination of blood levels of Damino acids as diagnostic and prognostic biomarkers. The experimental evidence of involvement of D-amino acids in various physiological pathways suggest investigating their levels in additional pathologies too, such as diabetes mellitus. In conclusion, the levels of D-amino acids in blood may represent novel diagnostic peripheral biomarkers for various disorders. Further studies are required to standardize/automatize the determinations and for confirming their clinical effectiveness.

Blood lead levels and risk factors among adolescents in Karbala Province

Karbala provides theoretical assistance for lead pollution prevention by determining blood levels and identifying relevant risk factors among adolescents. Blood lead levels determine by Graphite Furnace Atomic Absorb piton Spectrometry (GFAAS) result. Methods blood samples were taken from both males and females. A total of 100 subjects (average age of 13-17 years, 8 females, and 92 males) were included. The arithmetic means, sample characteristics between two levels of lead concentrations (Less than 100µg/L lead concentration and more or equal 100µg/L lead concentration were patients their number 50 and control also 50 Mean ± SE 49.36 ± 6.61 patients mean ± SE 184.18 ± 6.61 control. Education, His relationship with his parents, Living, Smoking. (T= 7.79**, 4.39**, 4.30**, 4.87**, resp.), while Samples Patients and control (T=18.86**).Conclusions. The levels of lead in the blood of adolescents 13 to 17 years in Karbala governorate were higher than in other areas due to leaving schools and working in different professions at an early age and living in unhealthy families.